Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging

Babak Behnam Azad; Vanessa Rota; Lihai Yu; Rebecca McGirr; André H.St Amant; Ting Yim Lee; Savita Dhanvantari; Leonard G. Luyt

doi:10.2310/7290.2014.00057

Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging

Babak Behnam Azad, Vanessa Rota, Lihai Yu, Rebecca McGirr, André H.St Amant, Ting Yim Lee, Savita Dhanvantari, Leonard G. Luyt

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution in various cell types of the pancreas in both strains of mice and receptor-specific uptake was confirmed by blocking with exendin-4. Biodistribution studies were carried out using ⁶⁸Galabeled GLP-1(7-37) peptides in CD1 and C57BL/6 mice. In addition, immunocompromised mice bearing GLP-1R-expressing insulinomas were evaluated by positron emission tomography (PET) imaging and ex vivo biodistribution studies. The optical GLP-1 probe strongly colocalized with immunofluorescence for insulin and glucagon, and more weakly with amylase (exocrine pancreas) and cytokeratin 19 (ductal cells), confirming its application for in situ GLP-1R imaging in various pancreatic cell types. Insulinomas were clearly visualized by in vivo PET. Reducing the peptide positive charge decreased renal retention as well as tumor uptake. Results demonstrate the application of the developed GLP-1 peptide analogues for in situ (optical) and in vivo (PET) imaging of GLP-1R expression.

Original language	English (US)
Pages (from-to)	1-16
Number of pages	16
Journal	Molecular imaging
Volume	14
Issue number	1
DOIs	https://doi.org/10.2310/7290.2014.00057
State	Published - Mar 1 2015
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Molecular Medicine
Biomedical Engineering
Radiology Nuclear Medicine and imaging
Condensed Matter Physics

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10.2310/7290.2014.00057

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title = "Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging",

abstract = "A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution in various cell types of the pancreas in both strains of mice and receptor-specific uptake was confirmed by blocking with exendin-4. Biodistribution studies were carried out using 68Galabeled GLP-1(7-37) peptides in CD1 and C57BL/6 mice. In addition, immunocompromised mice bearing GLP-1R-expressing insulinomas were evaluated by positron emission tomography (PET) imaging and ex vivo biodistribution studies. The optical GLP-1 probe strongly colocalized with immunofluorescence for insulin and glucagon, and more weakly with amylase (exocrine pancreas) and cytokeratin 19 (ductal cells), confirming its application for in situ GLP-1R imaging in various pancreatic cell types. Insulinomas were clearly visualized by in vivo PET. Reducing the peptide positive charge decreased renal retention as well as tumor uptake. Results demonstrate the application of the developed GLP-1 peptide analogues for in situ (optical) and in vivo (PET) imaging of GLP-1R expression.",

author = "Azad, {Babak Behnam} and Vanessa Rota and Lihai Yu and Rebecca McGirr and Amant, {Andr{\'e} H.St} and Lee, {Ting Yim} and Savita Dhanvantari and Luyt, {Leonard G.}",

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AU - Azad, Babak Behnam

AU - Rota, Vanessa

AU - Yu, Lihai

AU - McGirr, Rebecca

AU - Amant, André H.St

AU - Lee, Ting Yim

AU - Dhanvantari, Savita

AU - Luyt, Leonard G.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution in various cell types of the pancreas in both strains of mice and receptor-specific uptake was confirmed by blocking with exendin-4. Biodistribution studies were carried out using 68Galabeled GLP-1(7-37) peptides in CD1 and C57BL/6 mice. In addition, immunocompromised mice bearing GLP-1R-expressing insulinomas were evaluated by positron emission tomography (PET) imaging and ex vivo biodistribution studies. The optical GLP-1 probe strongly colocalized with immunofluorescence for insulin and glucagon, and more weakly with amylase (exocrine pancreas) and cytokeratin 19 (ductal cells), confirming its application for in situ GLP-1R imaging in various pancreatic cell types. Insulinomas were clearly visualized by in vivo PET. Reducing the peptide positive charge decreased renal retention as well as tumor uptake. Results demonstrate the application of the developed GLP-1 peptide analogues for in situ (optical) and in vivo (PET) imaging of GLP-1R expression.

AB - A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution in various cell types of the pancreas in both strains of mice and receptor-specific uptake was confirmed by blocking with exendin-4. Biodistribution studies were carried out using 68Galabeled GLP-1(7-37) peptides in CD1 and C57BL/6 mice. In addition, immunocompromised mice bearing GLP-1R-expressing insulinomas were evaluated by positron emission tomography (PET) imaging and ex vivo biodistribution studies. The optical GLP-1 probe strongly colocalized with immunofluorescence for insulin and glucagon, and more weakly with amylase (exocrine pancreas) and cytokeratin 19 (ductal cells), confirming its application for in situ GLP-1R imaging in various pancreatic cell types. Insulinomas were clearly visualized by in vivo PET. Reducing the peptide positive charge decreased renal retention as well as tumor uptake. Results demonstrate the application of the developed GLP-1 peptide analogues for in situ (optical) and in vivo (PET) imaging of GLP-1R expression.

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Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging

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